Intravascular catheters are among the most commonly used medical devices. Such catheters are routinely placed into a patient's vascular system for many procedures and often are left in place for extended periods. Since an intravascular catheter is a direct path from the outside environment to the patient's bloodstream, the catheter's presence presents a substantial and continuous potential for introduction of microorganisms into the patient's bloodstream. Practitioners have developed many protocols related to placement, use, attachment and detachment of fluid handling devices and other procedures related to catheters. The goal of almost all of these procedures is to avoid introduction of a microorganism into the patient's bloodstream. When a medicament is introduced into a patient through a catheter, the practitioner commonly follows the introduction with a flush solution that may include an anticoagulant such as heparin. The purpose of the flush solution is to move the medicament out of the catheter so that the entire dosage is delivered, and to leave a residual fill in the catheter so that the patient's blood does not back up in the catheter and possibly form a clot that would occlude the bore of the catheter. Thus, when the catheter is subsequently needed again, the properly flushed catheter is likely fully patent and ready for the next usage.
In 1988, Root, et al., published a study that reported on the effect of disodium ethylene diamine tetra acetic acid (EDTA), a compound well known for its chelating properties in vivo and widely used as an anticoagulant in vitro. The authors compared EDTA, heparin and vancomycin/heparin for effectiveness upon the growth of S. epidermis in vitro and its relation to infection prophylaxis of Hickman catheters in their report in Antimicrob. Agents Chemother., 32:1627-1631, 1988. Recently, Raad, et al. in U.S. Pat. No. 5,363,754 disclosed that pharmaceutical compositions of a mixture of minocycline and EDTA were useful in maintaining the patency of a catheter port. More recently, Raad, et al. in U.S. Pat. No. 5,688,516 further disclosed that effective catheter flush solutions could be prepared with non-glycopeptide antimicrobial agents other than vancomycin and a second agent selected form the group consisting of: (a) an anticoagulant, (b) an antithrombotic agent and (c) a chelating agent selected from a group of chelating agents. Raad, et al. teaches that since many antibiotic agents are not particularly stable at ambient conditions in aqueous solutions, that the disclosed compositions are stable and effective for about one month when stored under refrigerated conditions and that the solution should be brought to room temperature before administration to a patient. Alternatively, Raad, et al. teaches a kit including three compartments, the compartments containing the antimicrobial agent, the chelating, anticoagulant or antithrombotic agent and a diluent such as saline, Ringers solution or water so that the practitioner could mix the components prior to administration to the patient, thereby avoiding the reported stability problems.
While the disclosures of Raad, et al. teach a series of antimicrobial agents with a variety of other compounds, given the tendency of microorganisms to develop resistance to many antibiotic agents and the sensitivity to many people to certain antibiotics and other compounds, there still is a need for a catheter flush solution that does not include an antibiotic, is stable under ambient storage conditions and contains only materials with little likelihood of inducing an allergic response in a sensitive patient. Such a solution is disclosed hereinbelow.